The n e w e ng l a n d j o u r na l of m e dic i n e

Clinical Practice

Caren G. Solomon, M.D., M.P.H., Editor

HIV Infection — Screening, Diagnosis,

and Treatment
Michael S. Saag, M.D.​​

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence
­supporting various strategies is then presented, followed by a review of formal guidelines, when they exist.
The article ends with the author’s clinical recommendations.

A 28-year-old woman is brought to the emergency department after a motor vehicle From the University of Alabama at Bir-
collision. She has no clinically significant injuries other than a fractured radius. mingham, Birmingham. Address reprint
requests to Dr. Saag at the University of
A urine drug screen is positive for opioids and marijuana. As part of a universal Alabama at Birmingham, 845 19th St.
screening program, she undergoes testing for human immunodeficiency virus South, Bevill Biomedical Research Bldg.
(HIV) infection, and the results are positive. The patient is single and heterosexual, 256, Birmingham, AL 35294-2170, or at
msaag@uabmc.edu.
and she reports that she does not use injection drugs but occasionally trades sex for
drugs. She has not been tested for HIV previously. Her other routine laboratory stud- N Engl J Med 2021;384:2131-43.
DOI: 10.1056/NEJMcp1915826
ies are normal except for mild lymphopenia. How would you further evaluate and Copyright © 2021 Massachusetts Medical Society.
treat this patient?

The Cl inic a l Probl em

W
hen the acquired immunodeficiency syndrome (AIDS) was
first identified in the early 1980s, it was believed to be constrained to a
small number of risk groups.1 As more information became known
An audio version
about the epidemiologic picture of HIV transmission, it became clear that the in-
of this article
fection was transmitted primarily through sexual contact and blood (including is available at
through injection-drug use), as well as perinatally.2 In the United States, HIV type 1 NEJM.org
(HIV-1) is the predominant virus, whereas HIV type 2 (HIV-2) is endemic in other
areas of the world (e.g., West Africa).
In 2018, approximately 38,000 new cases of HIV infection were diagnosed in
the United States and its territories.3 Although perinatal transmission in the
United States has decreased to very low levels owing to routine screening for HIV
and initiation of antiretroviral therapy (ART) in HIV-infected women during preg-
nancy, cases in adolescents and adults decreased by just 7% between 2014 and
2018.4 Since the 1980s, the populations most affected by HIV infection have
changed, and HIV infection is now diagnosed disproportionately in persons who
are poor, disenfranchised, and have high barriers to medical care. In 2018, 21%
of new HIV infections were diagnosed in youths, 69% were diagnosed in men who
have sex with men, 10% in injection-drug users, 42% in Blacks, and 27% in per-
sons of Hispanic or Latino descent.3 A quarter of all new cases occur in White
persons, who make up 73% of the population.
An estimated 1 in 7 persons with HIV infection in the United States is unaware
of the infection.3 Many persons at risk — in particular, members of racial and
ethnic minorities — do not have regular access to health care and, therefore, do

n engl j med 384;22  nejm.org  June 3, 2021 2131

The New England Journal of Medicine
Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
 The n e w e ng l a n d j o u r na l of m e dic i n e

Key Clinical Points

HIV Infection — Screening, Diagnosis, and Treatment

• Despite extensive knowledge about human immunodeficiency virus (HIV), the number of cases of
incident HIV infection decreased by only 7% between 2014 and 2018.
• One in seven persons with HIV infection in the United States is unaware of the infection, and
transmission from these persons accounts for at least a third of new infections annually.
• Clinicians should test for HIV routinely in their practices, with repeat HIV testing in persons who
inject drugs, have multiple sexual partners, exchange sex for money or drugs, or have incident sexually
transmitted infections.
• Persons with a new diagnosis of HIV infection should be promptly referred to a clinical setting where a
full HIV assessment can be performed and antiretroviral therapy can be initiated rapidly.
• Long-term retention in care and maintenance of successful antiretroviral therapy allow persons with
HIV infection to have a near-normal life span and virtually eliminate transmission of HIV to others.

not receive a diagnosis until they present with
advanced disease, when treatments may be less
effective and the risk of death is highest.5
In 2019, the United States initiated the “End-
ing the HIV Epidemic” plan with a goal of reduc-
ing the number of new infections by 75% by
2025 and by 90% by 2030.6 The plan includes
four components: to identify all persons with
HIV infection, preferably early; to successfully
treat them with ART; to prevent new infections;
and to respond quickly to outbreaks as they oc-
cur. The foundation for the first two compo-
nents includes minimization of gaps in diag-
noses, improvement in linkage to care, rapid
initiation of therapy for HIV infection, and
maintenance of viral suppression through suc-
cessful retention in care.
S t r ategie s a nd E v idence
HIV Screening
U.S. guidelines recommend that all sexually ac-
tive persons be tested at least once for HIV7 and
that those who have an ongoing high risk of
infection be tested at least annually.8 Persons
with high risk are defined as those with an inci-
dent sexually transmitted infection; sexual part-
ners of persons with sexually transmitted infec-
tions; persons who have had more than one
sexual partner (or whose sexual partners have
had more than one partner) since their most
recent HIV test; injection-drug users; and per-
sons who exchange sex for money or drugs.
Testing is also recommended after the diagnosis
of incident sexually transmitted infections and
during pregnancy.
According to data from the National HIV
Surveillance System of the Centers for Disease
Control and Prevention (CDC), more than 75%
of persons in high-risk categories who had seen
a primary care provider within the previous year
were not offered an HIV test,5 and many patients
with undiagnosed HIV infection had multiple
health care visits before receiving an HIV test.9
This lack of testing is a failure of the health care
system, because each encounter is an opportu-
nity to reduce the incidence of HIV transmis-
sion. Up to 38% of new HIV infections are trans-
mitted by persons who are unaware of their HIV
status.10 Moreover, once HIV infection is identi-
fied and appropriately treated to maintain HIV
RNA levels below 200 copies per milliliter, pa-
tients can have a near-normal life span and do
not transmit the virus to others.11,12
Several studies have shown that in health care
settings (including emergency departments and
sexually transmitted disease and primary care
clinics), more HIV infections are identified with
the use of routine “opt-out” testing (i.e., all adult
patients are informed that an HIV test could be
performed, but they can opt out if they wish
to)13-16 than with physician-directed testing. Rec-
ommendations for opt-out testing have been in
place since 2006.7,17,18 Routine testing in the
emergency department has been shown to be
cost-effective.19
Diagnostic Tests
Many tests are available to accurately diagnose
HIV infection. The choice of the most appropri-
ate test for a given clinical presentation depends
on an understanding of the natural history of
HIV infection (i.e., which marker is present at a
given point after infection) (Fig. 1), the volume
of the specimen, and the test-performance spec-
ifications.20 During the “eclipse” period, before

2132 n engl j med 384;22  nejm.org  June 3, 2021

The New England Journal of Medicine

Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
 Clinical Pr actice

establishment of viremia at day 5, infection can-

not be detected. By days 6 to 8, virus can be Eclipse
detected by a nucleic acid amplification test Period HIV RNA
(NAAT). Viral proteins (p24 antigen) can be de-
tected between days 13 and 20. Antibodies, ini- IgG
HIV p24 antibody
tially in the form of IgM, are detectable by day antigen
20, and IgG is detectable by day 30. Most pa-
tients present long after the initial infection,
when tests for antibodies and nucleic acid are
both positive. IgM
antibody
Owing to the high cost of NAAT, combina-
tion antigen–antibody tests, which use p24 anti-
gen to identify patients in early stages of infec- X 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90

tion, are now the standard tests in hospital and
commercial laboratories. Most of these tests can
detect HIV-1 and HIV-2 infections. The CDC algo-
rithm for testing is shown in Figure 2.
Several available point-of-care rapid tests use
one of two techniques: lateral flow or flow-
through. Once antibodies bind to antigens, they
are detected by an indicator. Rapid tests can use
either whole blood (<10 to 50 μl) collected by
fingerstick or an oral swab as specimens; these
tests are convenient and easy to administer. Al-
though the sensitivity and specificity of these
tests are typically greater than 98%, laboratory-
based tests are more accurate, especially in early
infection, and they are required to confirm any
diagnosis made on the basis of a point-of-care
rapid test.
Linkage to Care
All persons who receive a diagnosis of HIV in-
fection should be referred for initiation of ART
and long-term follow-up. According to 2018
CDC surveillance data, only 78% of patients are
linked to care within 30 days after diagnosis,
and sustained viral suppression is achieved in
only 55 to 60% of persons (and a smaller per-
centage of infected adolescents and young
adults) with diagnosed HIV.21,22
The sooner that an initial clinic visit is sched-
uled after diagnosis, the more likely it is that the
patient will show up for the visit.23 One trial in
sub-Saharan Africa showed that “immediate”
initiation of ART at the time of a positive home-
based test increased follow-up with care.24 Simi-
lar findings related to immediate initiation of
therapy at the point of testing have been re-
ported in resource-rich countries, although struc- gency departments.25 In the United States, “rapid”
tural barriers often block implementation of initiation of ART, within 1 week after diagnosis,
immediate therapy, especially in hectic emer- is the recommended practice.11 Establishing an
Days after Infection Disseminates
NAAT
Test for p24 antigen
Test for IgM and
IgG antibodies
Test for IgG antibodies
Western blot test
Figure 1. Progression of HIV Viremia and Immune Response after Initial
Infection.
The time point X indicates the moment of initial exposure, and day 0 indi-
cates the establishment of infection. In most persons, exposure to human
immunodeficiency virus (HIV) does not result in infection or results in a
transient infection that does not become established; however, in persons
in whom long-term infection develops, the virus replicates in the exposed
tissues, expressing antigen on the surface of the infected cell or cells. An
immune response is mounted, with activated CD4 cells and macrophages
migrating to the site of infection. Ironically, these activated cells are the pri-
mary targets of HIV, and once infected, they generate a stronger immune
response, propagating further infection. This process takes 3 to 4 days after
exposure (during the “eclipse” period, which is defined as the time between
exposure and the ability to detect HIV RNA in plasma). Once a critical mass
of immune-system cells is reached, viral replication expands exponentially,
producing 10 to 100 billion virions per day. These viral particles (as mea-
sured by HIV RNA) can be detected as early as day 5 after establishment
of infection and peak at day 20, at which time a more effective immune re-
sponse begins to bring the infection under control. Viral antigen (p24 pro-
tein) can be detected at approximately day 14. Depending on the strength
of the immune response, symptoms of acute seroconversion syndrome
may manifest in the patient at approximately day 7 to day 12. Evidence of
the immune response can be detected by day 20 as IgM antibody positivity,
followed soon after by detectable serum IgG antibody. The time to reactiv-
ity for each diagnostic test is shown below the graph. Adapted from Hurt
et al.20 NAAT denotes nucleic acid amplification test.

n engl j med 384;22 nejm.org June 3, 2021 2133

The New England Journal of Medicine
Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
 The n e w e ng l a n d j o u r na l of m e dic i n e

Combination HIV-1 and HIV-2

antigen–antibody immunoassay

Nonreactive test result

Reactive test result
Negative for HIV-1 and HIV-2
antibodies and p24 antigen

HIV-1 and HIV-2 antibody HIV-1 NAAT if early infection

differentiation immunoassay suspected

Reactive test result for Nonreactive test result Reactive test result for Nonreactive test result
HIV-1 for HIV-1 HIV-1 for HIV-1 or indeter-
Nonreactive test result Reactive test result for Reactive test result for minate
for HIV-2 HIV-2 HIV-2 Nonreactive test result
for HIV-2 or indeter-
HIV-1 antibodies detected HIV-2 antibodies detected HIV antibodies detected minate

HIV-1 NAAT

Reactive test Nonreactive test

result for HIV-1 result for HIV-1

Acute HIV-1 infection Negative for HIV-1

Figure 2. Recommended Laboratory Testing to Detect HIV in Serum or Plasma Specimens.

Initial testing for HIV should be performed with a Food and Drug Administration–approved antigen–antibody im-
munoassay that detects HIV type 1 (HIV-1) and HIV type 2 (HIV-2) antibodies and HIV-1 p24 antigen. If the test is
nonreactive on the initial immunoassay, it is read as negative and no further testing is indicated unless there is clini-
cal suspicion of very early infection (before p24 antigen can be detected); in that case, an HIV-1 NAAT to detect HIV
RNA is performed. Specimens with a reactive antigen and antibody immunoassay result should be tested with a sup-
plemental antibody immunoassay that differentiates HIV-1 antibodies from HIV-2 antibodies; a reactive result on this
test is interpreted as positive for HIV-1 antibodies or HIV-2 antibodies, respectively. Specimens that are reactive on
the initial antigen and antibody assay but nonreactive (or indeterminate) with the HIV-1–specific and HIV-2–specific
antibody assay should be tested with an HIV-1 NAAT. A positive NAAT in this case is diagnostic of acute HIV-1 infec-
tion. A negative HIV-1 NAAT result and a nonreactive or indeterminate HIV-1 antibody differentiation immunoassay
result indicate an HIV-1 false positive result. Adapted from the Centers for Disease Control and Prevention (https://
stacks​.­cdc​.­gov/​­view/​­cdc/​­50872).

active relationship with the patient, providing
assistance in setting up the first appointment,
maintaining contact with the patient until the
first visit, and addressing any barriers to keep-
ing the first appointment (e.g., transportation)
are associated with an increased incidence of
linkage to treatment.26
Baseline Assessment and Initiation of ART
A comprehensive intake evaluation should be
performed at the initial visit. The items to be
covered in the first visit are provided in Table 1.
The history taking should focus on the risk to
other persons associated with exposure to the
patient as well as the patient’s sexual health,

2134 n engl j med 384;22  nejm.org  June 3, 2021

The New England Journal of Medicine

Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
 Clinical Pr actice
ongoing use of substances (including alcohol),
and mental health disorders. A physical exami-
nation should be performed to evaluate for signs
of advanced HIV infection such as thrush, vagi-
nal candidiasis, herpes simplex virus infection,
Kaposi’s sarcoma, lymphadenopathy, retinopathy,
mental status alterations, and wasting. Counsel-
ing should address the implications of an HIV
diagnosis, the importance of disclosure of the
patient’s HIV status to a few trusted friends or
relatives (for emotional support) and established
sexual partners, and potential barriers to keep-
ing future appointments (e.g., lack of transpor-
tation, food insecurity and lack of housing
[which may cause a person to prioritize day-to-
day survival over medical visits], and interper-
sonal violence). Specific topics of discussion
regarding prevention of transmission to others
should include the routine use of condoms dur-
ing sexual activity and avoidance of sharing
needles or other equipment during intravenous
drug use.
Patients should be reassured that they can
expect a near-normal life span27 and no risk of
transmission to others once viral suppression is
achieved and maintained with ART.12 From 2011
to 2017, among patients receiving standard ART
regimens, the incidence of death at 5 years after
diagnosis differed by only 2.7 percentage points
from that of age-matched controls.28
With rare exception, ART should be initiated
at the first clinic visit. The primary reason for
not initiating treatment is that the patient is
identified as an “elite controller”29,30 (i.e., a per-
son who has no detectable HIV RNA on presen-
tation) or is not ready to begin treatment for
personal reasons. Retention in care is improved
when ART is prescribed at the initial visit and
not delayed.31,32
T r e atmen t
Use of ART
The choice of initial therapy has been stream-
lined over the past 5 years (Table 2). Guidelines
suggest the use of an integrase strand-transfer
inhibitor (INSTI)–based therapy with tenofovir
(either tenofovir disoproxil fumarate [TDF] or
tenofovir alafenamide fumarate [TAF] formula-
tions) and either lamivudine (3TC) or emtricita­
bine (FTC).11,33 Often ART is prescribed before
n engl j med 384;22  nejm.org  June 3, 2021
The New England Journal of Medicine
Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
the availability of baseline laboratory results;
therefore, on the first visit, initial therapy should
be limited to either bictegravir–FTC–TAF or
dolutegravir plus a fixed-dose combination
(TDF–FTC, TDF–3TC, or TAF–FTC), owing to
their effectiveness, acceptable side-effect pro-
file, activity against hepatitis B virus (HBV),
and higher barrier to development of resistance
than other options. The regimens can be ad-
justed once the HIV RNA level, CD4 count, and
renal, liver, HBV, hepatitis C virus (HCV), and
HIV genotypic data are known. The data may
indicate that the treatment may be simplified
to a two-drug (dolutegravir–3TC) single tablet.11
Recommended ART treatments have yielded
greater than 90% sustained virologic suppres-
sion in clinical trials.11
The initiation of ART in patients with active
opportunistic infections or underlying condi-
tions and in pregnant women is beyond the
scope of this review. In general, the use of a
regimen that includes an INSTI that does not
require pharmacologic boosting with cobicistat
is typically the best choice in patients with these
conditions owing to the potency, pharmacoki-
netic profiles, and reduced drug–drug interac-
tions associated with these regimens. Prophylactic
therapy for opportunistic infections is summa-
rized in Table 3.11,34
Follow-up and Retention in Care
Follow-up visits should occur 4 to 6 weeks
after the initiation of ART and then every 3 to
4 months until virologic suppression is achieved.
Once suppression is sustained for a year, follow-
up visits should occur every 6 months.11 At each
visit, assessment of adherence to the ART regimen
and any adverse effects is essential. Any diffi-
culties with the regimen should be addressed
during the visit and, if warranted, the regimen
should be switched. Laboratory tests (Table 1)
should be performed, and the patient should be
evaluated for sexually transmitted infections,
ongoing use of substances (including alcohol),
mental health disorders, and barriers to main-
taining health (including housing issues, food
insecurity, domestic violence, and other social
determinants of care). Medication changes or
adjustments in dosages may be warranted if new
renal, hepatic, or hematologic abnormalities are
detected on laboratory tests. Counseling, ideally
2135
 Table 1. Evaluation and Screening in Persons with HIV Infection.*

2136
Test or Screening Procedure
Clinical evaluation
Clinical history taking
Physical examination
Screening test for HIV antibody and
antigen
Measurement of HIV RNA (viral
load)
CD4 count
At Diagnosis
Yes
Yes
Yes
Yes, if ART initiated at time and
place of diagnosis or if acute
HIV seroconversion sus-
pected
Yes, if ART initiated at time and
place of diagnosis or if acute
HIV seroconversion sus-
pected
At First Clinic Visit At Subsequent Visits With Regimen Change
Yes Yes Yes
Yes Yes Yes
Yes, but not needed if ART initiated Yes Yes
at time and place of diagnosis
Yes, but not needed if ART initiated Yes, every 6 mo until HIV RNA sus- Yes, at time of confirmed virologic
at time and place of diagnosis tained (<100 copies/ml) for 1 yr failure (detectable viremia)
and CD4 >250 cells/mm3; then no
longer check CD4 count (unless
The

HIV RNA is confirmed >200 cop-

Assessment of HIV resistance geno- Yes, if ART initiated at time and
type
Assessment of resistance to INSTIs
place of diagnosis; HIV RNA
obtained if acute HIV sero-
conversion suspected
No
ies/ml); CD4 count most valuable
early in course of treatment and
evaluation
Yes, but not needed if ART initiated No
at time and place of diagnosis
Yes, if known sexual partner is re- No
ceiving an INSTI
Yes, at time of confirmed virologic
failure (detectable viremia)
Yes, at time of confirmed virologic
failure (detectable viremia);
also if known sexual partner is
receiving an INSTI or if patient
is receiving an INSTI at time of
n e w e ng l a n d j o u r na l

The New England Journal of Medicine

virologic failure
of

Liver and kidney profile Yes Yes Yes Yes

Serum lipid profile No Yes Yes, only once per yr No

n engl j med 384;22  nejm.org  June 3, 2021

Complete blood count with differ- Yes Yes Yes Yes

Copyright © 2021 Massachusetts Medical Society. All rights reserved.

ential
m e dic i n e

Urinalysis No Yes Yes, only once per yr No

HBV serologic test No Yes Yes, perform again if any unexplained No
increase in serum AST or ALT level
or annually in patients who remain
at high risk for infection or reinfec-
tion (high-risk sexual exposure
or ongoing injection drug use);
in patients who were previously
infected and successfully treated,
perform HCV RNA screening tests

Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
 Test or Screening Procedure
HCV serologic test
Pregnancy test
Initiation of prophylaxis against
Pneumocystis jiroveci pneumonia
Cryptococcal antigen screening
Urine test for histoplasmosis antigen
Screening for sexually transmitted
At Diagnosis At First Clinic Visit
No Yes
No Yes, in women of child-bearing
potential
Yes, if ART initiated at time of di- Yes, according to guidelines when
agnosis and if P. jiroveci pneu- CD4 count is <200 cells/mm3
monia clinically suspected
(lymphopenia, wasting, oral
candidiasis)
No Yes, in all patients with CD4 counts
<100 cells/mm3 at diagnosis or
first clinic visit
No Yes, In patients with CD4 count
<100 cells/mm3 in areas where
histoplasmosis endemic
Yes, if ART initiated at time of di- Yes
At Subsequent Visits With Regimen Change
Yes, perform again if any unexplained No
increase in serum AST or ALT level
or annually in patients who remain
at high risk for infection or reinfec-
tion (high-risk sexual exposure
or ongoing injection drug use);
in patients who were previously
infected and successfully treated,
perform HCV RNA screening tests
Yes, in women of child-bearing poten- No
tial; evaluate as indicated
No Yes, in patients with virologic
failure
No Yes, only once per yr
No No
Yes, screen routinely (frequency of No
Clinical Pr actice

infection agnosis; screen at diagnosis testing depends on level of at-risk

or first clinic visit and rou- sexual activity)
tinely thereafter (frequency of
testing depends on level of

n engl j med 384;22  nejm.org  June 3, 2021

at-risk sexual activity)

The New England Journal of Medicine

Evaluation for cervical cancer No No Yes, annually (anal Pap smears, if No
available; digital rectal examina-
tion at a minimum)
Evaluation for anal cancer No No Yes, annually (anal Pap smears, if No
available; digital rectal examina-

Copyright © 2021 Massachusetts Medical Society. All rights reserved.

tion at a minimum)
Testing for HLA-B*5701 No Yes, perform before No Yes, perform before
prescribing abacavir prescribing abacavir
Tropism assay (CCR5) No Yes, perform before No Yes, perform before
prescribing maraviroc prescribing maraviroc
General screening to assess psycho-
social factors
Medication adherence No No Yes Yes
Substance use No Yes Yes No
Alcohol use No Yes Yes No
Depression, anxiety, or both No Yes Yes No

2137

Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
 The n e w e ng l a n d j o u r na l of m e dic i n e

in the same care facility, should be available if

* ALT denotes alanine aminotransferase, ART antiretroviral therapy, AST aspartate aminotransferase, HBV hepatitis B virus, HCV hepatitis C virus, HIV human immunodeficiency virus,
the patient has a new or recurring mental health
disorder.
With Regimen Change

Not all patients reach “undetectable” levels of

virus; some have a consistently maintained level
No

No

No
No
No
No

No

No
No
of virus between 50 and 100 copies per milliliter
owing to a large reservoir of latently infected
cells. In such patients, new replication is stopped
with ART and no further adjustment in treat-
ment is necessary. In contrast, if a viral load is
measured at more than 50 copies per milliliter
after previous viral suppression to 50 copies per
Yes, in patients >60 yr of age (or as

Yes, in patients >60 yr of age (or as

indicated clinically), every 2 yr

indicated clinically), every 2 yr milliliter or less, the measurement should be

At Subsequent Visits

quickly repeated, and medication adherence and

the side-effect profile should be assessed.11,33 A
confirmed HIV RNA level above 200 copies per
Yes

Yes
Yes
Yes, only once per yr

Yes, only once per yr

Yes, only once per yr
Yes, in patients with

milliliter should prompt assessment of viral re-

depression

sistance, including evaluation of INSTI resis-

tance if the patient is receiving an INSTI–based
ART regimen.
More than 85% of patients who consistently
receive care have sustained virologic suppression
indefinitely.35 After a year of stable viral suppres-
sion, clinical care typically transitions to pri-
At First Clinic Visit

mary care, and HIV becomes secondary in focus

during routine visits. Patients can receive care
Yes, in patients with

Yes

Yes
Yes
Yes
No

No

No
No

from both an HIV clinic and a primary care

provider, or primary care can be provided in the
depression

HIV clinic. Weight gain is common, especially

among patients who begin to receive an INSTI-
based regimen combined with TAF, although the
mechanism of weight gain remains incompletely
understood.36,37 Patients should be followed for
coexisting conditions, including obesity, diabetes
INSTI integrase strand-transfer inhibitor, and Pap Papanicolaou.

mellitus and other metabolic disorders, cancer,

At Diagnosis

and cardiovascular, renal, and hepatic disease.

No

No

No
No
No
No

No

No
No

These disorders occur more frequently and at a

younger age in patients with successfully treated
HIV infection than in age-matched controls.38

A r e a s of Uncer ta in t y
Sexual activity and exposure to sexu-

More than 42% of new HIV infections are trans-

mitted by persons who are known to be infected
ally transmitted infection
Test or Screening Procedure

with HIV but who are no longer receiving care10;

this fact underscores the need for effective strat-
Table 1. (Continued.)

egies for retention in care. Best practices to

Targeted screening

Domestic violence
Cognitive function

achieve this goal are still being developed. Cen-

Food insecurity

Social isolation
Polypharmacy

tralized care,39 the use of bilingual, bicultural

Suicidality

teams,40 clinic-based buprenorphine treatment for

Housing

Frailty

patients with concomitant opioid use disorder,41

specialized services for the transition from jail to

2138 n engl j med 384;22  nejm.org  June 3, 2021

The New England Journal of Medicine

Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
 Table 2. Current Recommended Initial Oral ART for Most Persons with HIV Infection.*

Regimen and Dose Frequency Adverse Effects Comments

Bictegravir– FTC–TAF Once daily as single-tablet Gastrointestinal symptoms (nausea, diar- Not recommended in patients with creatinine clearance <30 ml/min or
(50 mg/200 mg/25 mg) ­regimen rhea), headache, IRIS, lactic acidosis, Child–Pugh class C liver function; contraindicated with dofetilide or
hepatomegaly steatosis rifampin; avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbam-
azepine, and rifapentine; use with caution with metformin
Dolutegravir Once daily Gastrointestinal symptoms (nausea, diar- Not recommended in patients with creatinine clearance <30 ml/min or
(50 mg) rhea), headache, IRIS, lactic acidosis, Child–Pugh class C liver function; contraindicated with dofetilide; avoid
hepatomegaly steatosis divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine, and rifa-
pentine; use with caution with metformin
Plus TAF–FTC Once daily as single-tablet Gastrointestinal symptoms (nausea, Not recommended in patients with creatinine clearance <30 ml/min or
(25 mg/200 mg) ­regimen diarrhea), IRIS, lactic acidosis, hepato- Child–Pugh class B or C liver function; contraindicated with dofetilide;
megaly steatosis avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine,
and rifapentine; use with caution with metformin
Plus TDF–FTC Once daily as single-tablet Gastrointestinal symptoms (nausea, Not recommended in patients with creatinine clearance <30 ml/min or
(300 mg/200 mg) ­regimen diarrhea), IRIS, lactic acidosis, hepato- Child–Pugh class B or C liver function; contraindicated with dofetilide;
megaly steatosis avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine,
and rifapentine; use with caution with metformin
Plus TDF–3TC Individual tablets each once Gastrointestinal symptoms (nausea, Not recommended in patients with creatinine clearance <30 ml/min or
(300 mg/300 mg) daily diarrhea), IRIS, lactic acidosis, hepato- Child–Pugh class B or C liver function; contraindicated with dofetilide;
megaly steatosis avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine,
and rifapentine; use with caution with metformin
Dolutegravir–3TC Once daily as single-tablet Gastrointestinal symptoms (nausea, Do not use with lamivudine resistance (M184V or M184I mutation) or HBV
(50 mg/300 mg)† ­regimen (typically used diarrhea), IRIS, lactic acidosis, hepato- infection; not recommended in patients with creatinine clearance <30
after 12-wk lead-in period megaly steatosis ml/min or Child–Pugh class B or C liver function; contraindicated with
Clinical Pr actice

with other three-drug anti- dofetilide; avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbam-
retroviral regimen) azepine, and rifapentine; use with caution with metformin
Raltegravir Two tablets once daily Gastrointestinal symptoms (nausea, diar- Not recommended in patients with creatinine clearance <30 ml/min or
(600 mg)‡ rhea), headache, IRIS, lactic acidosis, Child–Pugh class B or C liver function; contraindicated with dofetilide;

n engl j med 384;22  nejm.org  June 3, 2021

The New England Journal of Medicine

hepatomegaly steatosis avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine,
and rifapentine; use with caution with metformin
Plus TAF–FTC Once daily as single-tablet Gastrointestinal symptoms (nausea, diar- Not recommended in patients with creatinine clearance <30 ml/min or
(25 mg/200 mg) ­regimen rhea), headache, IRIS, lactic acidosis, Child–Pugh class B or C liver function; contraindicated with dofetilide;
hepatomegaly steatosis avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine,
and rifapentine; use with caution with metformin

Copyright © 2021 Massachusetts Medical Society. All rights reserved.

Plus TDF–FTC Once daily as single-tablet Gastrointestinal symptoms (nausea, diar- Not recommended in patients with creatinine clearance <30 ml/min or
(300 mg/200 mg) ­regimen rhea), headache, IRIS, lactic acidosis, Child–Pugh class B or C liver function; contraindicated with dofetilide;
hepatomegaly steatosis avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine,
and rifapentine; use with caution with metformin
Plus TDF–3TC Individual tablets each once Gastrointestinal symptoms (nausea, diar- Not recommended in patients with creatinine clearance <30 ml/min or
(300 mg/300 mg) daily rhea), headache, IRIS, lactic acidosis, Child–Pugh class B or C liver function; contraindicated with dofetilide;
hepatomegaly steatosis avoid divalent cations (Ca++, Mg++, Fe++), phenytoin, carbamazepine,
and rifapentine; use with caution with metformin

* The Child–Pugh liver function scale is a three-category scale (A, B, or C), with C indicating the most severe compromise of liver function. Data are from the International Antiviral
Society–USA guidelines reported by Saag et al.11 FTC denotes emtricitabine, IRIS immune reconstitution inflammatory syndrome, TAF tenofovir alafenamide fumarate, TDF tenofovir
disoproxil fumarate, and 3TC lamivudine.
† Dolutegravir–3TC is not recommended for patients with rapid start of ART or for patients with chronic HBV infection, HIV RNA greater than 500,000 copies per milliliter, or a CD4 cell
count of less than 200 cells per cubic millimeter. Therapy is often initiated with one of the other regimens listed and then simplified to dolutegravir–3TC.

2139
‡ Raltegravir is included in the recommended regimen according to the Department of Health and Human Services guidelines reported by Scheer et al.32

Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
 2140
Table 3. Primary Prophylaxis against Opportunistic Infections in Persons with HIV Infection.

Indication and Regimen Dose, Route of Administration, and Frequency Adverse Effects Comments
Prophylaxis against P. jiroveki (CD4 count
<200 cells/mm3 or thrush)
The

Trimethoprim–sulfamethoxazole One double-strength tablet (160 mg of trim- Allergy, rash and erythroderma, rare
ethoprim and 800 mg of sulfamethoxazole) Stevens–Johnson syndrome, nausea,
daily or 3 times/wk diarrhea, anemia, neutropenia, hyper-
kalemia, drug-induced hepatitis
Dapsone 100 mg, orally once daily Rash, fever, methemoglobinemia, hemo- Used as alternative therapy
lysis
Pentamidine 300 mg, aerosolized through nebulizer monthly Bronchospasm, pancreatitis (rare) Used as third-line therapy; failure occurs as upper-
lobe P. jiroveci pneumonia
Atovaquone 1500 mg, orally (liquid suspension) daily Rash, gastrointestinal symptoms, head- Used as third-line therapy; must be given with
ache, insomnia food
Prophylaxis against cryptococcus (CD4 200 mg, orally once daily Rash, gastrointestinal symptoms, head- Serum cryptococcal antigen test recommended
count <100 cells/mm3 and posi- ache, alopecia, drug-induced hepatitis for all persons with newly diagnosed HIV
n e w e ng l a n d j o u r na l

tive serum cryptococcal antigen): (rare) infection and, if positive, lumbar puncture

The New England Journal of Medicine

of

fluconazole should be performed; in absence of meningi-

tis, initiate fluconazole
Prophylaxis against histoplasmosis (CD4 200 mg, orally once daily Gastrointestinal symptoms, rash, elevated Capsules administered with food or acidic drink

n engl j med 384;22  nejm.org  June 3, 2021

count <150 cells/mm3 in areas liver-enzyme levels, edema (e.g., cola)
where histoplasmosis is endemic

Copyright © 2021 Massachusetts Medical Society. All rights reserved.

m e dic i n e

only): itraconazole
Prophylaxis against Mycobacterium
avium complex: no longer recom-
mended in persons with rapid
initiation of ART

Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
 Clinical Pr actice

clinic,42 behavioral interventions,43 and enhanced C onclusions a nd

patient contact through navigator programs44
have been successful. Calling patients on the
telephone if they do not show up for scheduled
appointments is one of the most effective means
of retaining patients in care.44,45 An intervention
that involved brochures, posters, and short ver-
bal messages conveying the importance of con-
tinued health care visits was associated with a
higher incidence of return for subsequent ap-
pointments than no such intervention.46
With the success of ART over the past 2.5
decades, the population of persons with HIV in-
fection is aging. In the United States, more than
50% of the patients receiving care for HIV infec-
tion are older than 50 years of age; 18% are
older than 60 years, and older persons with HIV
infection are at higher risk for poor health out-
comes than persons of similar age without HIV
infection.27 Incident cardiovascular, kidney, neu-
rocognitive, and mental health disorders occur
at younger ages in persons with HIV infection
than in aged-matched controls. Older patients
with HIV infection tend to have worse outcomes
than younger patients because of the increased
likelihood of polypharmacy,47 frailty,48 social
isolation,49 and stigma.50 More data are needed
to guide the care of patients as they age.
Guidel ine s
Professional guidelines regarding screening,51-53
the selection of an ART regimen for individual
patients,11,33 and primary care for patients with
HIV infection54 are available. The recommenda-
tions presented here are concordant with these
guidelines.
R ec om mendat ions
The patient described in the vignette was at risk
for HIV infection owing to an opioid use disorder
and her engagement in sex in exchange for drugs.
The diagnosis through routine opt-out screening
in the emergency department underscores the
benefit of this approach, because otherwise the
diagnosis would probably have been made much
later. An appointment at an HIV clinic should be
scheduled within 1 week after diagnosis for a
baseline evaluation (a detailed social history tak-
ing and laboratory testing, including testing for
other sexually transmitted infections, and assess-
ment of the CD4 count and viral load) and
prompt initiation of ART, and she should be re-
ferred for management of substance abuse. She
should be counseled regarding disclosure of her
HIV status to trusted persons and sexual part-
ners, the importance of using condoms and
avoiding needle sharing to reduce disease trans-
mission, the need to continue to receive ART as
prescribed and to return for follow-up, and the
expectation of a near normal life span if viral
suppression is achieved and maintained. In sub-
sequent appointments, adherence to and any ad-
verse effects of ART, as well as substance use
and other social factors that might interfere with
adherence to ongoing treatment, should be rou-
tinely assessed.
Dr. Saag reports receiving grant support, paid to his institu-
tion, from ViiV Healthcare and Gilead Sciences. No other po-
tential conflict of interest relevant to this article was reported.
Disclosure forms provided by the author are available with the
full text of this article at NEJM.org.
I thank Bonnie Zarzaur for technical assistance and Donna
Jacobsen for editorial assistance with an earlier draft of the
manuscript.

References
1. Update on acquired immune deficiency
syndrome (AIDS) — United States. MMWR
Morb Mortal Wkly Rep 1982;​ 31:​507-8,
513-4.
2. Centers for Disease Control and Pre-
vention. Ways HIV can be transmitted
(https://www​.­cdc​.­gov/​­h iv/​­basics/​­h iv​
-­t ransmission/​­ways​-­people​-­get​-­hiv​.­html).
3. Centers for Disease Control and Pre-
vention. HIV: basic statistics (https://www​
.­cdc​.­gov/​­hiv/​­basics/​­statistics​.­html).
4. Peters H, Francis K, Sconza R, et al.
UK mother-to-child HIV transmission
rates continue to decline: 2012-2014. Clin
Infect Dis 2017;​64:​527-8.
5. Dailey AF, Hoots BE, Hall HI, et al.
Human immunodeficiency virus testing
and diagnosis delays — United States.
MMWR Morb Mortal Wkly Rep 2017;​66:​
1300-6.
6. HIV.gov. What is Ending the HIV Epi-
demic in the U.S.? 2021 (https://www​.­hiv​.­gov/​
­federal​-­response/​­ending​-­the​-­hiv​-­epidemic/​
­overview).
7. Branson BM, Handsfield HH, Lampe
MA, et al. Revised recommendations for
HIV testing of adults, adolescents, and
pregnant women in health-care settings.
MMWR Recomm Rep 2006;​ 55(RR-14):​
1-17.
8. DiNenno EA, Prejean J, Irwin K, et al.
Recommendations for HIV screening of
gay, bisexual, and other men who have
sex with men — United States, 2017.
MMWR Morb Mortal Wkly Rep 2017;​66:​
830-2.
9. Nakao JH, Wiener DE, Newman DH,
Sharp VL, Egan DJ. Falling through the
cracks? Missed opportunities for earlier
HIV diagnosis in a New York City hospi-
tal. Int J STD AIDS 2014;​25:​887-93.
10. Li Z, Purcell DW, Sansom SL, Hayes
D, Hall HI. HIV transmission along the
continuum of care — United States, 2016.
MMWR Morb Mortal Wkly Rep 2019;​68:​
267-72.
11. Saag MS, Gandhi RT, Hoy JF, et al.
Antiretroviral drugs for treatment and

n engl j med 384;22  nejm.org  June 3, 2021 2141

The New England Journal of Medicine
Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
 The n e w e ng l a n d j o u r na l
prevention of HIV infection in adults:
2020 recommendations of the Interna-
tional Antiviral Society-USA Panel. JAMA
2020;​324:​1651-69.
12. Rodger AJ, Cambiano V, Bruun T, et al.
Sexual activity without condoms and risk
of HIV transmission in serodifferent cou-
ples when the HIV-positive partner is us-
ing suppressive antiretroviral therapy.
JAMA 2016;​316:​171-81.
13. Prekker ME, Gary BM, Patel R, et al.
A comparison of routine, opt-out HIV
screening with the expected yield from
physician-directed HIV testing in the ED.
Am J Emerg Med 2015;​33:​506-11.
14. Haukoos JS, Hopkins E, Conroy AA,
et al. Routine opt-out rapid HIV screening
and detection of HIV infection in emer-
gency department patients. JAMA 2010;​
304:​284-92.
15. Henriquez-Camacho C, Villafuerte-
Gutierrez P, Pérez-Molina JA, Losa J, Go-
tuzzo E, Cheyne N. Opt-out screening
strategy for HIV infection among patients
attending emergency departments: system-
atic review and meta-analysis. HIV Med
2017;​18:​419-29.
16. Haukoos J, Hopkins E. HIV screening
in the emergency department: thoughts
on disparities and the next step in ending
the epidemic. J Am Coll Emerg Physicians
Open 2020;​1:​484-6.
17. Chin T, Hicks C, Samsa G, McKellar
M. Diagnosing HIV infection in primary
care settings: missed opportunities. AIDS
Patient Care STDS 2013;​27:​392-7.
18. Hsieh Y-H, Kelen GD, Beck KJ, et al.
Evaluation of hidden HIV infections in an
urban ED with a rapid HIV screening pro-
gram. Am J Emerg Med 2016;​34:​180-4.
19. Mwachofi A, Fadul NA, Dortche C,
Collins C. Cost-effectiveness of HIV screen-
ing in emergency departments: a system-
atic review. AIDS Care 2020 September 15
(Epub ahead of print).
20. Hurt CB, Nelson JAE, Hightow-Weid-
man LB, Miller WC. Selecting an HIV test:
a narrative review for clinicians and re-
searchers. Sex Transm Dis 2017;​44:​739-
46.
21. Centers for Disease Control and Pre-
vention. HIV and youth. April 2020
(https://www​.­cdc​.­gov/​­h iv/​­pdf/​­g roup/​­age/​
­youth/​­cdc​-­hiv​-­youth​.­pdf).
22. Centers for Disease Control and Pre-
vention. Diagnoses of HIV infection in
the United States and dependent areas,
2018 (updated). HIV surveillance report.
Vol. 31. May 2020 (https://www​.­cdc​.­gov/​
­h iv/​­pdf/​­l ibrary/​­reports/​­surveillance/​­cdc​
-­hiv​-­surveillance​-­report​-­2018​-­updated​-­vol​
-­31​.­pdf).
23. Gardner EM, McLees MP, Steiner JF,
Del Rio C, Burman WJ. The spectrum of
engagement in HIV care and its relevance
to test-and-treat strategies for prevention
of HIV infection. Clin Infect Dis 2011;​52:​
793-800.
2142 n engl j med 384;22  nejm.org  June 3, 2021
The New England Journal of Medicine
Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.
of m e dic i n e
24. Labhardt ND, Ringera I, Lejone TI,
et al. Effect of offering same-day ART vs
usual health facility referral during home-
based HIV testing on linkage to care and
viral suppression among adults with HIV
in Lesotho: The CASCADE randomized
clinical trial. JAMA 2018;​319:​1103-12.
25. Colasanti J, Sumitani J, Mehta CC,
et al. Implementation of a rapid entry pro-
gram decreases time to viral suppression
among vulnerable persons living with
HIV in the southern United States. Open
Forum Infect Dis 2018;​5(6):​ofy104.
26. Mugavero MJ, Lin H-Y, Allison JJ, et al.
Failure to establish HIV care: character-
izing the “no show” phenomenon. Clin
Infect Dis 2007;​45:​127-30.
27. Marcus JL, Leyden WA, Alexeeff SE,
et al. Comparison of overall and comor-
bidity-free life expectancy between in-
sured adults with and without HIV infec-
tion, 2000-2016. JAMA Netw Open 2020;​
3(6):​e207954.
28. Edwards J, Cole S, Breger T, et al.
Mortality among people entering HIV
care compared to the general US popula-
tion: an observational study. Ann Intern
Med (in press).
29. Crowell TA, Gebo KA, Blankson JN,
et al. Hospitalization rates and reasons
among HIV elite controllers and persons
with medically controlled HIV infection.
J Infect Dis 2015;​211:​1692-702.
30. Promer K, Karris MY. Current treat-
ment options for HIV elite controllers:
a review. Curr Treat Options Infect Dis
2018;​10:​302-9.
31. Ford N, Migone C, Calmy A, et al.
Benefits and risks of rapid initiation of
antiretroviral therapy. AIDS 2018;​ 32:​
17-
23.
32. Scheer S, Hsu L, Schwarcz S, et al.
Trends in the San Francisco human im-
munodeficiency virus epidemic in the
“Getting to Zero” era. Clin Infect Dis
2018;​66:​1027-34.
33. HIV.gov. Guidelines for the use of anti-
retroviral agents in adults and adolescents
living with HIV. 2019 (https://clinicalinfo​
.­hiv​.­gov/​­en/​­guidelines/​­adult​-­and​-­adolescent​
-­arv/​­initiation​-­antiretroviral​-­t herapy).
34. HIV.gov. Guidelines for the prevention
and treatment of opportunistic infections
in adults and adolescents with HIV. 2019
(https://clinicalinfo​.­hiv​.­gov/​­en/​­g uidelines/​
­adult​-­a nd​-­adolescent​-­opportunistic​
-­i nfection/​­mycobacterium​-­avium​
-­complex​-­disease?view=full).
35. Centers for Disease Control and Pre-
vention. Monitoring selected national HIV
prevention and care objectives by using
HIV surveillance data — United States
and 6 dependent areas, 2018. HIV surveil-
lance supplemental report. Vol. 25. No.
2. May 2020 (https://www​.­cdc​.­gov/​­h iv/​
­pdf/​­l ibrary/​­reports/​­surveillance/​­cdc​-­h iv​
-­surveillance​-­supplemental​-­report​-­vol​-­25​
-­2​.­pdf).
36. Sax PE, Erlandson KM, Lake JE, et al.
Weight gain following initiation of anti-
retroviral therapy: risk factors in random-
ized comparative clinical trials. Clin In-
fect Dis 2020;​71:​1379-89.
37. Bakal DR, Coelho LE, Luz PM, et al.
Obesity following ART initiation is com-
mon and influenced by both traditional
and HIV-/ART-specific risk factors. J Anti-
microb Chemother 2018;​73:​2177-85.
38. Pahwa S, Deeks S, Zou S, et al. NIH
workshop on HIV-associated comorbidi-
ties, coinfections, and complications: sum-
mary and recommendation for future re-
search. J Acquir Immune Defic Syndr
2021;​86:​11-8.
39. Davila JA, Miertschin N, Sansgiry S,
Schwarzwald H, Henley C, Giordano TP.
Centralization of HIV services in HIV-
positive African-American and Hispanic
youth improves retention in care. AIDS
Care 2013;​25:​202-6.
40. Enriquez M, Farnan R, Cheng A-L,
et al. Impact of a bilingual/bicultural care
team on HIV-related health outcomes.
J Assoc Nurses AIDS Care 2008;​19:​295-
301.
41. Lucas GM, Chaudhry A, Hsu J, et al.
Clinic-based treatment of opioid-depen-
dent HIV-infected patients versus referral
to an opioid treatment program: a ran-
domized trial. Ann Intern Med 2010;​152:​
704-11.
42. Myers JJ, Kang Dufour M-S, Koester
KA, et al. The effect of patient navigation
on the likelihood of engagement in clinical
care for HIV-infected individuals leaving
jail. Am J Public Health 2018;​108:​385-92.
43. Modi R, Amico KR, Knudson A, et al.
Assessing effects of behavioral interven-
tion on treatment outcomes among pa-
tients initiating HIV care: rationale and
design of iENGAGE intervention trial.
Contemp Clin Trials 2018;​69:​48-54.
44. Gardner LI, Giordano TP, Marks G,
et al. Enhanced personal contact with HIV
patients improves retention in primary
care: a randomized trial in 6 US HIV clin-
ics. Clin Infect Dis 2014;​59:​725-34.
45. Eaton EF, Saag MS, Mugavero M. En-
gagement in human immunodeficiency
virus care: linkage, retention, and antiret-
roviral therapy adherence. Infect Dis Clin
North Am 2014;​28:​355-69.
46. Gardner LI, Marks G, Craw JA, et al. A
low-effort, clinic-wide intervention im-
proves attendance for HIV primary care.
Clin Infect Dis 2012;​55:​1124-34.
47. Edelman EJ, Rentsch CT, Justice AC.
Polypharmacy in HIV: recent insights and
future directions. Curr Opin HIV AIDS
2020;​15:​126-33.
48. Verheij E, Kirk GD, Wit FW, et al.
Frailty is associated with mortality and
incident comorbidity among middle-aged
human immunodeficiency virus (HIV)-
positive and HIV-negative participants.
J Infect Dis 2020;​222:​919-28.
 Clinical Pr actice

49. Greysen SR, Horwitz LI, Covinsky KE,
Gordon K, Ohl ME, Justice AC. Does so-
cial isolation predict hospitalization and
mortality among HIV+ and uninfected
older veterans? J Am Geriatr Soc 2013;​61:​
1456-63.
50. Lam A, Mayo NE, Scott S, Brouillette
M-J, Fellows LK. HIV-related stigma af-
fects cognition in older men living with
HIV. J Acquir Immune Defic Syndr 2019;​
80:​198-204.
51. Brown SR, Kennelly C. AAFP recom-
mends universal screening for HIV infec-
tion beginning at age 18 years of age. Am
Fam Physician 2014;​89:​614-7.
52. Qaseem A, Snow V, Shekelle P, Hop-
kins R Jr, Owens DK. Screening for HIV in
health care settings: a guidance state-
ment from the American College of Physi-
cians and HIV Medicine Association. Ann
Intern Med 2009;​150:​125-31.
53. U.S. Preventive Services Task Force.
Human immunodeficiency virus (HIV) in-
fection: screening. Final recommendation
statement. June 11, 2019 (https://www​
.­uspreventiveservicestaskforce​.­org/​­uspstf/​
­recommendation/​­human​-­immunodeficiency​
-­virus​-­hiv​-­infection​-­screening).
54. Thompson MA, Horberg MA, Agwu
AL, et al. Primary care guidance for per-
sons with human immunodeficiency virus:
2020 update by the HIV Medicine Associa-
tion of the Infectious Diseases Society of
America. Clin Infect Dis 2020 November 6
(Epub ahead of print).
Copyright © 2021 Massachusetts Medical Society.

images in clinical medicine

The Journal welcomes consideration of new submissions for Images in Clinical
Medicine. Instructions for authors and procedures for submissions can be found
on the Journal’s website at NEJM.org. At the discretion of the editor, images that
are accepted for publication may appear in the print version of the Journal,
the electronic version, or both.

n engl j med 384;22  nejm.org  June 3, 2021 2143

The New England Journal of Medicine
Downloaded from nejm.org at UNIVERSIDAD PERUANA CAYETANO HEREDIA on September 4, 2021. For personal use only. No other uses without permission.
Copyright © 2021 Massachusetts Medical Society. All rights reserved.